What is prostate cancer?
The prostate is a male reproductive gland about the size of a walnut. Its major function is to make a milky fluid that mixes with sperm to form semen. The prostate lies just below the bladder in front of the rectum and surrounds the urethra, the tube that carries urine and semen through the penis and out of the body. The growth and activity of the prostate is controlled by male sex hormones called androgens, which are mainly produced by the testicles. Prostate cancer begins when cells in the prostate gland start to grow uncontrollably. Almost all prostate cancers are adenocarcinomas, meaning that they develop from the glandular cells that make and secrete the milky prostatic fluid. Prostate cancer that keeps growing even when levels of testosterone in the body are very low and that spreads beyond the prostate gland to other tissues (e.g., lymph nodes, bones, liver, lung) is called metastatic castration-resistant prostate cancer (mCRPC).
If you have been diagnosed with prostate cancer, you are not alone. Prostate cancer is the most common cancer among men living in the United States. About 1 in 7 men will be diagnosed with prostate cancer at some point in their lifetime.
It is normal to feel concerned and confused about what to do next after hearing you have prostate cancer. Over the past two decades, there has been much progress in the understanding of how prostate cancer develops and spreads, new treatment options have become available and many more are currently being studied. Learning as much as you can about available treatment options, including clinical trials, and being involved in choosing the right option for you may be helpful to you. There are many helpful websites that provide education about prostate cancer as well as information about support groups. Some are listed here.
One group of potential treatment options, the poly (ADP-ribose) polymerase (PARP) inhibitors, are being explored in clinical studies involving men with advanced prostate cancer who have certain genetic markers in their tumor DNA. The list of genetic markers that may indicate if a patient’s prostate cancer will respond to PARP inhibitors includes BRCA1, BRCA2 and ATM most commonly, but also BARD1, BRIP1, CDK12, CHEK2, FANCA, NBN, PALB2, RAD51, RAD51B, RAD51C, RAD51D, and RAD54L. These genes are involved in a type of DNA repair called homologous recombination. When one of these genes is altered, the cell is said to have homologous recombination deficiency (HRD). There are laboratory tests available that can detect these markers to help determine which patients may be candidates for PARP inhibitors.
How Can Homologous Recombination Deficiency (HRD) Testing Guide Treatment Decisions in Prostate Cancer?
Deoxyribonucleic acid (DNA) is the material inside the genes of all living organisms that determines how they look and how their bodies function. Damage to DNA such as alterations (changes that result in an error in the sequence of DNA, and the inability of some cells to repair this damage) may result in an increased likelihood that the affected cells will become cancerous. In addition to causing cancer, damage to DNA and/or proteins involved in DNA repair pathways can promote the growth of some cancers. Identifying alterations that impair the process of DNA repair can identify patients at risk for developing certain cancers and, in addition, these tests may help identify treatment options for patients with some types of cancer.
Genetic tests are available that can identify DNA alterations involved in the DNA-repair pathway called homologous recombination repair alterations. These alterations can impact the ability of the cell to repair the damage to the DNA strand. These genetic alterations include BRCA1, BRCA2, ATM, and others (listed above). Positive tests for these alterations may be associated with more aggressive forms of some cancers, including prostate cancer. These tests are called homologous recombinant deficiency (HRD) tests. Such tests are being studied along with investigational treatments to determine whether they may help physicians develop personalized treatment approaches and to select treatment options that may be more likely to benefit patients with prostate cancer. For example, tumors with BRCA1, BRCA2 or ATM alterations may be more likely to respond to some types of chemotherapy and investigational drugs like PARP inhibitors that are currently being studied for the treatment of prostate cancer. There are specific diagnostic kits available that physicians can use to perform these tests, and clinical trials and hospital laboratories often have testing available too. These tests may be performed on blood, saliva, or tumor tissue collected from a surgical procedure or from a biopsy procedure.
For more information about genetic testing in cancer visit the National Cancer Institute website: